1. Field of the Invention
This invention relates to novel heterocyclic substituted phenoxyalkylpyrazines, to methods of preparation thereof and to methods of use thereof as antipicornaviral agents; and to intermediates in their preparation and the use of those intermediates as antipicornaviral agents.
2. Information Disclosure Statement
U.S. Pat. No. 4,857,539 to Diana et al., issued Aug. 15, 1989, discloses compounds of the formula; ##STR2## wherein:
Y is an alkylene bridge of 3-9 carbon atoms;
Z is N or HC:
R is hydrogen or lower-alkyl of 1-5 carbon atoms, with the proviso that when Z is N, R is lower-alkyl;
R.sub.1 and R.sub.2 are hydrogen, halogen, lower-alkyl, lower-alkoxy, nitro, lower-alkoxycarbonyl or trifluoromethyl; and
Het is selected from; ##STR3## which are stated to be useful as antiviral agents.
U.S. Pat. No. 4,861,791 to Diana et al., issued Aug. 29, 1989 discloses compounds of the formula: ##STR4## wherein R to R.sub.8 represent various radicals and y. The compounds are stated to be useful as antiviral agents, in particular against picornaviruses.
U.S. Pat. No. 5,242,924, to Diana, issued Sep. 7, 1993 from application filed Jul. 2, 1992, discloses compounds of the formula: ##STR5## wherein
Y is a bond, or C.sub.1 -C.sub.6 alkylene;
R.sub.1 is hydrogen or C.sub.1 -C.sub.3 lower-alkyl;
R.sub.2 and R.sub.3 are each independently hydrogen, C.sub.1 -C.sub.3 lower-alkyl or halogen;
R.sub.4 is hydrogen, or C.sub.1 -C.sub.3 lower-alkyl; or pharmaceutically acceptable acid addition salts thereof which are stated to be useful as antiviral agents, particularly against picornaviruses.
European Patent Application 435381, published Jul. 3, 1991, discloses pyridazinamines of formula: ##STR6## wherein
R.sub.1 is hydrogen, C.sub.1-4 alkyl, halo, hydroxy, trifluoromethyl, cyano, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1 -alkylsulfinyl, C.sub.1-4 alkylsulfonyl, C.sub.1-4 alkyloxycarbonyl, C.sub.1 -alkylcarbonyl or aryl;
R.sub.2 and R.sub.3 are hydrogen or C.sub.1-4 alkyl;
Alk is C.sub.1-4 alkanediyl;
R.sub.4 and R.sub.5 are hydrogen, C.sub.1-4 alkyl or halo; and
Het is ##STR7## wherein
R.sub.6 is hydrogen, C.sub.1-6 alkyl; hydroxyC.sub.1-6 alkyl; C.sub.3-6 cycloalkyl; aryl; arylC.sub.1-4 alkyl; C.sub.1-4 alkyloxyC.sub.1-4 alkyl; C.sub.3-6 cyclo- alkylC.sub.1-4 alkyl; trifluoromethyl or amino;
each R.sub.7 independently is hydrogen; C.sub.1-6 alkyl; C.sub.3-6 cyclo-alkyl; aryl; arylC.sub.1-4 alkyl; C.sub.1-4 alkyloxyC.sub.1-4 alkyl; C.sub.3-6 cyclo- alkylC.sub.1-4 alkyl or trifluoromethyl; and
each aryl independently is phenyl or phenyl substituted with 1 or 2 substituents each independently selected from halo, C.sub.1-4 alkyl, trifluoromethyl, C.sub.1-4 alkyloxy or hydroxy. The compounds are stated to have antiviral activity.